tbuckley/cabot-search huggingface dataset:
Multi-organ landscape of therapy-resistant melanoma
Authors: Sixue Liu, Prashanthi Dharanipragada, Shirley H. Lomeli, Yan Wang, Xiao Zhang, Zhentao Yang, Raymond J. Lim, Camelia Dumitras, Philip O. Scumpia, Steve M. Dubinett, Gatien Moriceau, Douglas B. Johnson, Stergios J. Moschos, Roger S. Lo
Journal: Nature Medicine (2023)

Abstract Metastasis and failure of present-day therapies represent the most common causes of mortality in patients with cutaneous melanoma. To identify the underlying genetic and transcriptomic landscapes, in this study we analyzed multi-organ metastases and tumor-adjacent tissues from 11 rapid autopsies after treatment with MAPK inhibitor (MAPKi) and/or immune checkpoint blockade (ICB) and death due to acquired resistance. Either treatment elicits shared genetic alterations that suggest immune-evasive, cross-therapy resistance mechanisms. Large, non-clustered deletions, inversions and inter-chromosomal translocations dominate rearrangements. Analyzing data from separate melanoma cohorts including 345 therapy-naive patients and 35 patients with patient-matched pre-treatment and post-acquired resistance tumor samples, we performed cross-cohort analyses to identify MAPKi and ICB as respective contributors to gene amplifications and deletions enriched in autopsy versus therapy-naive tumors. In the autopsy cohort, private/late mutations and structural variants display shifted mutational and rearrangement signatures, with MAPKi specifically selecting for signatures of defective homologous-recombination, mismatch and base-excision repair. Transcriptomic signatures and crosstalks with tumor-adjacent macroenvironments nominated organ-specific adaptive pathways. An immune-desert, CD8 + -macrophage-biased archetype, T-cell exhaustion and type-2 immunity characterized the immune contexture. This multi-organ analysis of therapy-resistant melanoma presents preliminary insights with potential to improve therapeutic strategies.
Dynamic chromatin accessibility licenses STAT5- and STAT6-dependent innate-like function of TH9 cells to promote allergic inflammation
Authors: Aran Son, Francoise Meylan, Julio Gomez-Rodriguez, Zenia Kaul, McKella Sylvester, Guido H. Falduto, Estefania Vazquez, Tamara Haque, Moses M. Kitakule, Chujun Wang, Kalpana Manthiram, Chen-Feng Qi, Jun Cheng, Rama K. Gurram, Jinfang Zhu, Pamela Schwartzberg, Joshua D. Milner, Pamela A. Frischmeyer-Guerrerio, Daniella M. Schwartz
Journal: Nature Immunology (2023)
A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals
Authors: Wei Ouyang, Wei Lu, Yamin Zhang, Yiming Liu, Jong Uk Kim, Haixu Shen, Yunyun Wu, Haiwen Luan, Keith Kilner, Stephen P. Lee, Yinsheng Lu, Yiyuan Yang, Jin Wang, Yongjoon Yu, Amy J. Wegener, Justin A. Moreno, Zhaoqian Xie, Yixin Wu, Sang Min Won, Kyeongha Kwon, Changsheng Wu, Wubin Bai, Hexia Guo, Tzu-li Liu, Hedan Bai, Giuditta Monti, Jason Zhu, Surabhi R. Madhvapathy, Jacob Trueb, Maria Stanslaski, Elizabeth M. Higbee-Dempsey, Iwona Stepien, Nayereh Ghoreishi-Haack, Chad R. Haney, Tae-il Kim, Yonggang Huang, Roozbeh Ghaffari, Anthony R. Banks, Thomas C. Jhou, Cameron H. Good, John A. Rogers
Journal: Nature Biomedical Engineering (2023)
Screening hydrogels for antifibrotic properties by implanting cellularly barcoded alginates in mice and a non-human primate
Authors: Sudip Mukherjee, Boram Kim, Lauren Y. Cheng, Michael David Doerfert, Jiaming Li, Andrea Hernandez, Lily Liang, Maria I. Jarvis, Peter D. Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Trisha Ray, Tanguy Terlier, Cody Fell, Ping Song, Roberto N. Miranda, Jose Oberholzer, David Yu Zhang, Omid Veiseh
Journal: Nature Biomedical Engineering (2023)
Ethnic diversity fosters the social integration of refugee students
Authors: Zsófia Boda, Georg Lorenz, Malte Jansen, Petra Stanat, Aileen Edele
Journal: Nature Human Behaviour (2023)

Forced migration has become a global megatrend, and many refugees are school aged. As social integration is key to their wellbeing and success, it is pivotal to determine factors that promote the social integration of refugee youth within schools. Here, using a large, nationally representative social network dataset from Germany, we examine the relationships of refugee adolescents with their peers (304 classrooms, 6,390 adolescents and 487 refugees). We find that refugee adolescents have fewer friends and are more often rejected as desk mates than their classmates. Crucially, however, they are less rejected in more diverse classrooms. This results from two basic processes: (1) more opportunities to meet other ethnic minority peers, who are more accepting of refugees in general and (2) higher acceptance of refugee adolescents by ethnic majority peers in more diverse settings. Our results can help promote the social adjustment of young refugees in school and mitigate the negative consequences of prejudice.
1H magnetic resonance spectroscopic imaging of deuterated glucose and of neurotransmitter metabolism at 7 T in the human brain
Authors: Petr Bednarik, Dario Goranovic, Alena Svatkova, Fabian Niess, Lukas Hingerl, Bernhard Strasser, Dinesh K. Deelchand, Benjamin Spurny-Dworak, Martin Krssak, Siegfried Trattnig, Gilbert Hangel, Thomas Scherer, Rupert Lanzenberger, Wolfgang Bogner
Journal: Nature Biomedical Engineering (2023)
A living biobank of patient-derived ductal carcinoma in situ mouse-intraductal xenografts identifies risk factors for invasive progression
Authors: Stefan J. Hutten, Roebi de Bruijn, Catrin Lutz, Madelon Badoux, Timo Eijkman, Xue Chao, Marta Ciwinska, Michael Sheinman, Hendrik Messal, Andrea Herencia-Ropero, Petra Kristel, Lennart Mulder, Rens van der Waal, Joyce Sanders, Mathilde M. Almekinders, Alba Llop-Guevara, Helen R. Davies, Matthijs J. van Haren, Nathaniel I. Martin, Fariba Behbod, Serena Nik-Zainal, Violeta Serra, Jacco van Rheenen, Esther H. Lips, Lodewyk F.A. Wessels, Jelle Wesseling, Colinda L.G.J. Scheele, Jos Jonkers
Journal: Cancer Cell (2023)

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC). Due to a lack of biomarkers able to distinguish high- from low-risk cases, DCIS is treated similar to early IBC even though the minority of untreated cases eventually become invasive. Here, we characterized 115 patient-derived mouse-intraductal (MIND) DCIS models reflecting the full spectrum of DCIS observed in patients. Utilizing the possibility to follow the natural progression of DCIS combined with omics and imaging data, we reveal multiple prognostic factors for high-risk DCIS including high grade, HER2 amplification, expansive 3D growth, and high burden of copy number aberrations. In addition, sequential transplantation of xenografts showed minimal phenotypic and genotypic changes over time, indicating that invasive behavior is an intrinsic phenotype of DCIS and supporting a multiclonal evolution model. Moreover, this study provides a collection of 19 distributable DCIS-MIND models spanning all molecular subtypes.
Landscape and future directions of machine learning applications in closed-loop brain stimulation
Authors: Anirudha S. Chandrabhatla, I. Jonathan Pomeraniec, Taylor M. Horgan, Elizabeth K. Wat, Alexander Ksendzovsky
Journal: npj Digital Medicine (2023)

Abstract Brain stimulation (BStim) encompasses multiple modalities (e.g., deep brain stimulation, responsive neurostimulation) that utilize electrodes implanted in deep brain structures to treat neurological disorders. Currently, BStim is primarily used to treat movement disorders such as Parkinson’s, though indications are expanding to include neuropsychiatric disorders like depression and schizophrenia. Traditional BStim systems are “open-loop” and deliver constant electrical stimulation based on manually-determined parameters. Advancements in BStim have enabled development of “closed-loop” systems that analyze neural biomarkers (e.g., local field potentials in the sub-thalamic nucleus) and adjust electrical modulation in a dynamic, patient-specific, and energy efficient manner. These closed-loop systems enable real-time, context-specific stimulation adjustment to reduce symptom burden. Machine learning (ML) has emerged as a vital component in designing these closed-loop systems as ML models can predict / identify presence of disease symptoms based on neural activity and adaptively learn to modulate stimulation. We queried the US National Library of Medicine PubMed database to understand the role of ML in developing closed-loop BStim systems to treat epilepsy, movement disorders, and neuropsychiatric disorders. Both neural and non-neural network ML algorithms have successfully been leveraged to create closed-loop systems that perform comparably to open-loop systems. For disorders in which the underlying neural pathophysiology is relatively well understood (e.g., Parkinson’s, essential tremor), most work has involved refining ML models that can classify neural signals as aberrant or normal. The same is seen for epilepsy, where most current research has focused on identifying optimal ML model design and integrating closed-loop systems into existing devices. For neuropsychiatric disorders, where the underlying pathologic neural circuitry is still being investigated, research is focused on identifying biomarkers (e.g., local field potentials from brain nuclei) that ML models can use to identify onset of symptoms and stratify severity of disease.
Obstructive sleep apnoea, nocturnal hypoxaemia, and cognitive decline in elderly patients
Authors: AbdelKebir Sabil, Frédéric Gagnadoux
Journal: European Respiratory Journal (2023)

Major neurocognitive disorder (MND) is a clinical disorder with currently no curative treatment. Formerly known as dementia, MND interferes with the independence and daily life of patients, causing an impairment of both daytime functioning and sleep quality, leading to disability and death [1, 2]. There is a strong link between the prevalence of MND and advancing age in what is termed late-onset dementia [3]. In fact, more than 80% of MND occurs in individuals aged 65 years or older [4]. Obstructive sleep apnoea could represent a modifiable risk factor of major neurocognitive disorder in elderly patients <http://bit.ly/3SQXA73>
Trends in COVID-19-associated mortality in patients with pulmonary hypertension: a COMPERA analysis
Authors: Kai-Helge Schmidt, Katrin Milger, Christine Pausch, Doerte Huscher, David Pittrow, Ekkehard Grünig, Gerd Staehler, Henning Gall, Oliver Distler, Dirk Skowasch, Michael Halank, Heinrike Wilkens, Matthias Held, Hans Klose, Marius M. Hoeper
Journal: European Respiratory Journal (2023)

Patients with pulmonary hypertension (PH) have been among those affected heavily by the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Early case series reported case fatality rates ranging from 19–45% in small series of 11–70 patients with PH who contracted COVID-19 [1–4]. A prospective series of 211 French patients with various forms of PH, who developed COVID-19 between February 2020 and April 2021, found an overall case fatality rate of 24.6% [5]. In patients with pulmonary hypertension, the mortality rate associated with COVID-19 has declined sharply with the emergence of the Omicron variants <https://bit.ly/42OMsfj>
“Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: effect of probiotics.” M. Badran, A. Khalyfa, A.C. Ericsson, C. Puech, Z. McAdams, S.B. Bender and D. Gozal.<i>Eur Respir J</i>2023; 61: 2200002.
Journal: European Respiratory Journal (2023)

In the methods and results section of the above-mentioned study, the authors refer to VSL#3, which was used in their study and which is a commercial probiotic containing eight bacterial strains manufactured by Alfasigma.In the discussion section, other studies are discussed that have used a commercial probiotic formulation, also referred to as VSL#3.The authors wish to make readers aware that these formulations are not the same and the studies mentioned in the discussion section used a different formulation of VSL#3, currently named "De Simone Formulation" and manufactured and distributed by Exegi and Visbiome, respectively.
Another piece in the pirfenidone puzzle
Authors: Mareike Lehmann, Martin Kolb
Journal: European Respiratory Journal (2023)

<b>An editorial discussing the recent article by Ma and co-workers that contributes another puzzle piece to the mechanism of action for pirfenidone with elegant <i>in vitro</i> and <i>in situ</i> studies, and importantly, using a clinically relevant drug concentration</b>https://bit.ly/40Vi0zr
<i>SMARCAL1</i>: Expanding the spectrum of genes associated with alternative lengthening of telomeres
Authors: Cristiane M Ida, Robert B Jenkins
Journal: Neuro-Oncology (2023)

Journal Article SMARCAL1: Expanding the spectrum of genes associated with alternative lengthening of telomeres Get access Cristiane M Ida, Cristiane M Ida Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA https://orcid.org/0000-0003-2768-2913 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert B Jenkins Robert B Jenkins Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA Corresponding Author: Robert B. Jenkins, MD, PhD, Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA (rjenkins@mayo.edu). https://orcid.org/0000-0002-4049-694X Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 9, September 2023, Pages 1576–1577, https://doi.org/10.1093/neuonc/noad084 Published: 27 April 2023 Article history Published: 27 April 2023 Corrected and typeset: 10 May 2023
Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology
Authors: Marco Metra, Daniela Tomasoni, Marianna Adamo, Antoni Bayes‐Genis, Gerasimos Filippatos, Magdy Abdelhamid, Stamatis Adamopoulos, Stefan D. Anker, Laura Antohi, Michael Böhm, Frieder Braunschweig, Tuvia Ben Gal, Javed Butler, John G.F. Cleland, Alain Cohen‐Solal, Kevin Damman, Finn Gustafsson, Loreena Hill, Ewa A. Jankowska, Mitja Lainscak, Lars H. Lund, Theresa McDonagh, Alexandre Mebazaa, Brenda Moura, Wilfried Mullens, Massimo Piepoli, Piotr Ponikowski, Amina Rakisheva, Arsen Ristic, Gianluigi Savarese, Petar Seferovic, Rajan Sharma, Carlo Gabriele Tocchetti, Mehmet Birhan Yilmaz, Cristiana Vitale, Maurizio Volterrani, Stephan von Haehling, Ovidiu Chioncel, Andrew J.S. Coats, Giuseppe Rosano
Journal: European Journal of Heart Failure (2023)
Mitogen-induced defective mitosis transforms neural progenitor cells
Authors: Hiba K Omairi, Cameron J Grisdale, Mathieu Meode, Alexandra K Bohm, Sophie Black, Nancy J Adam, Cassidy P Chapman, Tatiana Maroilley, John J Kelly, Maja Tarailo-Graovac, Steven J M Jones, Michael D Blough, John Gregory Cairncross
Journal: Neuro-Oncology (2023)

Abstract Background Chromosome instability (CIN) with recurrent copy number alterations is a feature of many solid tumors, including glioblastoma (GBM), yet the genes that regulate cell division are rarely mutated in cancers. Here, we show that the brain-abundant mitogen, platelet-derived growth factor-A (PDGFA) fails to induce the expression of kinetochore and spindle assembly checkpoint genes leading to defective mitosis in neural progenitor cells (NPCs). Methods Using a recently reported in vitro model of the initiation of high-grade gliomas from murine NPCs, we investigated the immediate effects of PDGFA exposure on the nuclear and mitotic phenotypes and patterns of gene and protein expression in NPCs, a putative GBM cell of origin. Results NPCs divided abnormally in defined media containing PDGFA with P53-dependent effects. In wild-type cells, defective mitosis was associated with P53 activation and cell death, but in some null cells, defective mitosis was tolerated. Surviving cells had unstable genomes and proliferated in the presence of PDGFA accumulating random and clonal chromosomal rearrangements. The outcome of this process was a population of tumorigenic NPCs with recurrent gains and losses of chromosomal regions that were syntenic to those recurrently gained and lost in human GBM. By stimulating proliferation without setting the stage for successful mitosis, PDGFA-transformed NPCs lacking P53 function. Conclusions Our work describes a mechanism of transformation of NPCs by a brain-associated mitogen, raising the possibility that the unique genomic architecture of GBM is an adaptation to defective mitosis that ensures the survival of affected cells.
CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure
Authors: Tushuai Li, Yue Gu, Baocai Xu, Kamil Kuca, Jie Zhang, Wenda Wu
Journal: Molecular Cancer (2023)

Abstract CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution in RCC remain elusive. We confirmed the overexpression of circZBTB44 in RCC cells compared to normal kidney cell HK-2. CircZBTB44 knockdown suppressed the viability, proliferation, and migration of RCC cells and inhibited tumorigenesis in xenograft mouse models. Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) and Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) are two RNA binding proteins of circZBTB44. HNRNPC facilitated the translocation of circZBTB44 from nuclei to cytoplasm via m6A modification, facilitating the interaction of IGF2BP3 and circZBTB44 in the cytoplasm of RCC cells. Furthermore, circZBTB44 upregulated Hexokinase 3 (HK3) expression by binding to IGF2BP3 in RCC cells. HK3 exerted oncogenic effects on RCC cell malignant behaviors and tumor growth. In the co-culture of RCC cells with macrophages, circZBTB44 promoted M2 polarization of macrophages by up-regulating HK3. In summary, HNRNPC mediated circZBTB44 interaction with IGF2BP3 to up-regulate HK3, promoting the proliferation and migration of RCC cells in vitro and tumorigenesis in vivo . The results of the study shed new light on the targeted therapy of RCC.
Changes in COVID-19-related mortality across key demographic and clinical subgroups in England from 2020 to 2022: a retrospective cohort study using the OpenSAFELY platform
Authors: Linda Nab, Edward P K Parker, Colm D Andrews, William J Hulme, Louis Fisher, Jessica Morley, Amir Mehrkar, Brian MacKenna, Peter Inglesby, Caroline E Morton, Sebastian C J Bacon, George Hickman, David Evans, Tom Ward, Rebecca M Smith, Simon Davy, Iain Dillingham, Steven Maude, Ben F C Butler-Cole, Thomas O’Dwyer, Catherine L Stables, Lucy Bridges, Christopher Bates, Jonathan Cockburn, John Parry, Frank Hester, Sam Harper, Bang Zheng, Elizabeth J Williamson, Rosalind M Eggo, Stephen J W Evans, Ben Goldacre, Laurie A Tomlinson, Alex J Walker
Journal: The Lancet Public Health (2023)
Commentary
Authors: Amit Mehta, Mouen A. Khashab
Journal: Endoscopy (2023)

Refractory bronchobiliary fistula (BBF) is a rare complication that frequently poses a significant therapeutic challenge. Given the high morbidity and mortality associated with surgical fistulectomy, conservative interventions are still preferred. In this video, Didden et al. demonstrate the treatment of a refractory bronchobiliary fistula via endoscopic retrograde cholangiography, with the use of both embolization coils and glue. Previous reports have described the successful use of endoscopic or percutaneous embolization with glue and coil for refractory bile leak, with a clinical success rate of 78 % to 100 % [1] [2] [3]. In this case, the authors used Histoacryl (n-butyl-2-cyanoacrylate) glue, which offers a more rapid polymerization time in comparison to alternatives such as Dermabond (2-octyl-2-cyanoacrylate), thereby lowering the risk of glue migration outside the fistula [4]. The authors also used a straight cannulation to inject the glue. However, an extraction balloon catheter that can occlude the bile duct during injection may better prevent glue migration outside the fistula. Ultimately, minimally invasive alternatives to the management of BBF, such as described here, offer promising benefits to patients in whom first-line management has failed and further investigation is warranted.
Sex as a Biological Variable in Tissue Engineering and Regenerative Medicine
Authors: Josephine B. Allen, Christopher Ludtka, Bryan D. James
Journal: Annual Review of Biomedical Engineering (2023)

Although sex differences have been noted in cellular function and behavior, therapy efficacy, and disease incidence and outcomes, the adoption of sex as a biological variable in tissue engineering and regenerative medicine remains limited. Furthering the development of personalized, precision medicine requires considering biological sex at the bench and in the clinic. This review provides the basis for considering biological sex when designing tissue-engineered constructs and regenerative therapies by contextualizing sex as a biological variable within the tissue engineering triad of cells, matrices, and signals. To achieve equity in biological sex within medicine requires a cultural shift in science and engineering research, with active engagement by researchers, clinicians, companies, policymakers, and funding agencies.
No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta
Authors: Julius Hollnberger, Yang Liu, Simin Xu, Silvia Chang, Ross Martin, Savrina Manhas, Thomas Aeschbacher, Bin Han, Tahmineh Yazdi, Lindsey May, Dong Han, Alex Shornikov, John Flaherty, Dmitry Manuilov, Vithika Suri, Tarik Asselah, Pietro Lampertico, Heiner Wedemeyer, Soo Aleman, Christopher Richards, Roberto Mateo, Evguenia Maiorova, Tomas Cihlar, Hongmei Mo, Stephan Urban
Journal: Journal of Hepatology (2023)